Latent tuberculosis infection (LTBI) affects one-fourth of the worlds population. Hematopoietic stem cell transplantation (HSCT) recipients are at an elevated risk of developing active tuberculosis infection (ATBI). In this retrospective study of donors and HSCT recipients who underwent transplantation between February 2000 and June 2018, our aim was to determine the prevalence of LTBI and ATBI and to describe diagnostic and therapeutic strategies in an HSCT population in an endemic region. The cohort of 409 participants included 125 allogeneic HSCT (allo-HSCT) recipients, 165 autologous HSCT (auto-HSCT) recipients, and 119 HSCT donors. Patients were evaluated pre-HSCT with tuberculin skin test and thoracic imaging. LTBI was diagnosed in 26.2% of the cohort. Cases represented 20% of the auto-HSCT population, 20% of the allo-HSCT population, and 41.2% of the donor population. Pre-HSCT evaluation to rule out ATBI was performed in 62.6% of the cohort; all results were negative. Isoniazid was administered to 73.3% of those with LTBI. Within subgroups, 91.7% of HSCT recipients and 51% of donors received treatment. The median duration of therapy pre-HSCT was 70 days in recipients and 48 days in donors. The incidence of post-HSCT ATBI was 0 at 1-year follow-up. The incidence of LTBI in our population was higher than expected and still might have been underestimated owing to diagnostic test limitations. The absence of incident ATBI suggests that recipients, as opposed to donors, must receive LTBI treatment. Prevention of infectious complications in the HSCT population should be prioritized to improve clinical outcomes. Prospective data from collaborative working groups is needed to determine the best diagnostic and therapeutic approaches in this vulnerable patient population.
Allo-HSCT continues to have a role in the therapy of a selected group of high-risk adult patients with ALL in CR1. Although the clinical significance of MRD has been studied less extensively in adults with ALL than in children, recent studies support its role as the strongest prognostic factor that can identify patients that are unlikely to be cured by standard chemotherapy and benefit from undergoing allo-HSCT. In addition, MRD status both pre- and post-HSCT has been found to correlate directly with the risk of relapse. Currently, the clinical challenge consists on applying MRD and molecular failure to integrate novel agents and immunotherapy to lower MRD before allo-HSCT and to modulate the graft versus leukemia (GVL) effect after transplant.
Eculizumab is effective for complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome. Although lifelong therapy had been suggested, discontinuation does not universally lead to relapse. Comprehensive data evaluating risk factors for recurrence following discontinuation is limited. Our aim was to systematically review available literature assessing the role of complement genetic variants in this setting. Reports on CM-TMA and eculizumab withdrawal published before January 1st, 2021 were included. Key reasons for patient exclusion were no follow-up after drug withdrawal and patients lacking complement genetic testing. Two-hundred and eighty patients from 40 publications were included. Median age was 28 years-old and 25 patients had a known history of renal transplant. Complement genetic variants were identified in 60%, most commonly in CFH (n=59) and MCP/CD46 (n=38). Of patients with a complement gene variant, 51.3% had ≥1 likely pathogenic/pathogenic variant, while the remaining had variants of uncertain significance. Overall relapse rate after therapy discontinuation was 29.6%. Relapse rate was highest among patients with CFH variants and MCP/CD46 variants in canonical splice regions. Variants of uncertain significance (p<0.001) and likely pathogenic/pathogenic variants (p<0.001) were associated with increased relapse. Presence of a renal allograft (p=0.009); decreasing age (p=0.029); and detection of variants in CFH (p<0.001), MCP/CD46 (p<0.001) or C3 (p<0.001) were all independently associated with relapse after eculizumab discontinuation. Eculizumab discontinuation is appropriate in specific patients with CM-TMA. Caution should be exerted when attempting such a strategy in patients with high risk of recurrence, including a subgroup of patients with MCP/CD46 variants.
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